CN109678687B - Efficient preparation method of o-hydroxyacetophenone compound - Google Patents
Efficient preparation method of o-hydroxyacetophenone compound Download PDFInfo
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- CN109678687B CN109678687B CN201811513188.4A CN201811513188A CN109678687B CN 109678687 B CN109678687 B CN 109678687B CN 201811513188 A CN201811513188 A CN 201811513188A CN 109678687 B CN109678687 B CN 109678687B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
Abstract
The invention discloses an efficient preparation method of an o-hydroxyacetophenone compound, which comprises the following steps: substituted phenol and acetic anhydride react at the temperature of 130-150 ℃ in the molar ratio of 1:1-1.1 under the solvent-free condition to generate acetic acid substituted phenyl ester, and acetic acid and the acetic acid substituted phenyl ester are separated by rectification; the prepared phenyl acetate substitutes transposition reaction in an organic solvent at 50-120 ℃ under the action of a catalyst to generate the o-hydroxyacetophenone compound shown in the formula, after the reaction is finished, the catalyst is removed by filtration, the solvent is evaporated, and the o-hydroxyacetophenone compound is prepared by rectification under vacuum; the catalyst is phosphomolybdic acid, phosphotungstic acid, silicotungstic acid or a mixture thereof. The preparation method disclosed by the invention is mild in condition, simple in process, high in selectivity, environment-friendly and suitable for industrial production, and the ortho-position selectivity is up to 99.5%.
Description
Technical Field
The invention relates to the technical field of organic compound synthesis, in particular to a high-efficiency preparation method of an o-hydroxyacetophenone compound.
Background
The o-hydroxyacetophenone compound is an important organic chemical raw material, and particularly the o-hydroxyacetophenone can be used for synthesizing the Ia antiarrhythmic drug propafenone hydrochloride.
Esterification and friedel-crafts rearrangement reactions are classical organic synthesis reactions. The traditional method is that firstly phenol is esterified with acetyl chloride or acetic anhydride to generate phenyl acetate, and then the phenyl acetate is put into AlCl3The rearrangement reaction occurs catalytically. The conventional method has a ratio of ortho-para to para-69, and most of the product is para-product.
The mechanism of fries reaction is as follows:
because the acyl cation generated in the next reaction has two positions which can be selected, the selectivity of the product is not very high. At present, no effective method for efficiently preparing the ortho-position product exists.
Disclosure of Invention
In order to solve the technical problems, the invention provides a high-efficiency preparation method of an o-hydroxyacetophenone compound, so as to achieve the purpose of preparing a high-selectivity ortho-position product by using an environment-friendly catalyst.
In order to achieve the purpose, the technical scheme of the invention is as follows:
an efficient preparation method of o-hydroxyacetophenones compounds comprises the following steps:
(1) reacting substituted phenol with a structure shown as a formula (I) with acetic anhydride according to a molar ratio of 1:1-1.1 at 130-150 ℃ in the absence of a solvent to generate acetic acid substituted phenyl ester with a structure shown as a formula (II), and separating acetic acid from the acetic acid substituted phenyl ester (II) by rectification;
(2) the prepared acetic acid substituted phenyl ester (II) is subjected to transposition reaction in an organic solvent at 50-120 ℃ under the action of a catalyst to generate an o-hydroxyacetophenone compound with the structure shown in the formula (III), after the reaction is finished, the catalyst is removed by filtration, the solvent is evaporated, and the o-hydroxyacetophenone compound (III) is prepared by rectification under vacuum; the catalyst is phosphomolybdic acid, phosphotungstic acid, silicotungstic acid or a mixture thereof;
the reaction formula is as follows:
in the formula (I), the compound is shown in the specification,
y is hydrogen, alkyl, alkoxy, phenyl or substituted phenyl, halogen, nitro, cyano, or pyridyl.
In the above scheme, the organic solvent in step (2) is dichloromethane, dichloroethane or chlorobenzene.
In the scheme, the mass ratio of the acetic acid substituted phenyl ester (II) to the catalyst is 100: 5-200.
By the technical scheme, the efficient preparation method of the o-hydroxyacetophenone compound provided by the invention uses phosphomolybdic acid, phosphotungstic acid, silicotungstic acid or a mixture thereof as a catalyst, and a transition intermediate is formed due to a multi-element complex center, the reaction mechanism is probably a synergistic reaction, and a product is directly generated without an acyl positive ion, so that the o-position product has good selectivity, and the reaction mechanism is as follows:
compared with the prior art, the invention has the advantages of high selectivity of the ortho-position product up to 99.5 percent, reasonable process route, cheap and easily obtained raw materials, low cost, environmental protection, and easy industrialization and serialization.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below.
The invention provides an efficient preparation method of an o-hydroxyacetophenone compound, which comprises the following specific embodiments:
example 1:
adding 100g of phenol and 114g of acetic anhydride into a flask, slowly heating while stirring, heating to 145 ℃ for reaction for 2.5 hours, starting rectification, and distilling off acetic acid. Raising the temperature to 180 ℃ until no fraction is produced, and then raising the temperature to collect the main fraction to obtain phenyl acetate which is directly used for the next reaction.
Adding 50g of phenyl acetate, 100ml of dichloroethane and 5g of phosphomolybdic acid into a flask, heating to 70 ℃ for reaction for 7 hours, cooling to 40 ℃, filtering to remove the catalyst (which can be recycled), and distilling the filtrate to remove the dichloroethane to obtain a crude o-hydroxyacetophenone. The crude o-hydroxyacetophenone is rectified and purified under vacuum, and the product after rectification temperature stabilization is collected, so that the o-hydroxyacetophenone with the purity of over 99.5 percent can be obtained.
1HNMR(500MHZ,CDCl3)δ:2.609(3H)，6.89(1H)，6.96(1H)，7.45(1H)，7.71(1H)，12.25(1H)。
Example 2:
adding 116g of o-cresol and 114g of acetic anhydride into a flask, slowly heating while stirring, heating to 150 ℃, reacting for 3 hours, starting rectification, and distilling off acetic acid. Raising the temperature to 180 ℃ until no fraction is produced, and then raising the temperature to collect the main fraction to obtain the o-toluyl acetate which is directly used for the next reaction.
60g of o-toluyl acetate, 100ml of dichloromethane and 10g of phosphotungstic acid are added into a flask, the mixture is heated to 80 ℃ for reaction for 6 hours, the temperature is reduced to 40 ℃, the catalyst is removed by filtration (can be recycled), and the dichloromethane is removed by distillation of the filtrate, so that the crude product of the 2-hydroxy-3-methylacetophenone is obtained. The crude product of 2-hydroxy-3-methylacetophenone is rectified and purified under vacuum, and the product after the rectification temperature is stable is collected, so that the purity of 2-hydroxy-3-methylacetophenone is more than 99.5%.
1HNMR(500MHZ,CDCl3)δ:2.26(3H,s)，2.63(3H,s)，6.81(1H,t)，7.34(1H,d)，7.59(1H,d)，12.51(1H,s)。
Example 3:
132g of o-methoxyphenol and 114g of acetic anhydride are added into a flask, the mixture is slowly heated to 135 ℃ under stirring, the reaction is carried out for 2 hours, then the rectification is started, and the acetic acid is distilled off. Raising the temperature to 180 ℃ until no fraction is produced, and then raising the temperature to collect the main fraction to obtain o-methoxyphenyl acetate which is directly used for the next reaction.
Adding 60g of o-methoxyphenyl acetate, 100ml of chlorobenzene and 8g of silicotungstic acid into a flask, heating to 90 ℃, reacting for 8 hours, cooling to 40 ℃, filtering to remove the catalyst (which can be recycled), and distilling the filtrate to remove the chlorobenzene to obtain a crude product of the 2-hydroxy-3-methoxyacetophenone. The crude product of 2-hydroxy-3-methoxyacetophenone is rectified and purified under vacuum, and the product after rectification temperature stabilization is collected, so that the 2-hydroxy-3-methoxyacetophenone with purity of over 99.5 percent can be obtained.
1HNMR(500MHZ,CDCl3)δ:2.632(3H,s)，3.898(3H,s)，6.840(1H,t)，7.054(1H,d)，7.336(1H,d)，12.558(1H,d)。
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (1)
1. An efficient preparation method of o-hydroxyacetophenone compounds is characterized by comprising the following steps:
(1) reacting substituted phenol with a structure shown as a formula (I) with acetic anhydride according to a molar ratio of 1:1-1.1 at 130-150 ℃ in the absence of a solvent to generate acetic acid substituted phenyl ester with a structure shown as a formula (II), and separating acetic acid from the acetic acid substituted phenyl ester (II) through rectification;
(2) the prepared acetic acid substituted phenyl ester (II) is subjected to transposition reaction in an organic solvent at 50-120 ℃ under the action of a catalyst to generate an o-hydroxyacetophenone compound with the structure shown in the formula (III), after the reaction is finished, the catalyst is removed by filtration, the solvent is evaporated, and the o-hydroxyacetophenone compound (III) is prepared by rectification under vacuum; the catalyst is silicotungstic acid;
the reaction formula is as follows:
（Ⅰ） （Ⅱ） （Ⅲ）
in the formula, Y is hydrogen, alkyl, alkoxy or phenyl;
the organic solvent in the step (2) is dichloromethane, dichloroethane or chlorobenzene;
the mass ratio of the acetic acid substituted phenyl ester (II) to the catalyst is 100: 5-200.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102093189A (en) * | 2009-12-09 | 2011-06-15 | 曹日庆 | Method for preparing o-hydroxyacetophenone and p-hydroxyacetophenone |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093189A (en) * | 2009-12-09 | 2011-06-15 | 曹日庆 | Method for preparing o-hydroxyacetophenone and p-hydroxyacetophenone |
Non-Patent Citations (2)
| Title |
|---|
| Fries rearrangement of aryl esters catalysed by heteropoly acid;Elena F. Kozhevnikova等;《Applied Catalysis A: General》;20030530;第245卷(第1期);第71页第2.4节、第72页表2 * |
| 乙酸苯酯合成的动力学研究;蔡广乐等;《化工中间体》;20070315;第22页第1.2节、第27页结论部分 * |
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